Our specific goal of this project is to develop therapeutically useful antimicrobial peptides and understand the mechanism of action of these peptides on microbial pathogens. Our immediate goal is to emphasize the mycobacteria due to recent emergence of resistant strains of Mycobacterium tuberculosis. The intuition and the belief in the success of this goal is from the encouraging preliminary results on the activity of a few cecropin analogs tested on the non pathogenic strain, Mycobacterium smegmatis 655. Our aim is to design and synthesize antimicrobial cecropin hybrid analogs, using our principal tool solid- phase peptide synthesis and also a new approach of combinatorial methods of chemical synthesis to create molecular libraries with immense diversity. The mechanism of action of these peptides will be studied by conductivity measurements, solid-state NMR, and assays for activity of analogs containing structural changes such as chirality, direction of the amide bond, sequence, pseudo peptide linkages and conformational restriction.